The goal of these studies will be to understand the role of the intestinal environment on influencing the responses of CD4+ T cells to oral proteins. Mucosal surfaces such as the intestine are exposed to a wide array of exogenous antigen (Ag). The introduction of Ag in these tissues leads to a tightly-regulated cascade of events that result in distinct local and systemic responses. CD4+ T cells play a critical role in coordinating these responses by directing activities of other cell types through the release of specific arrays of lymphokines. A better understanding of how CD4+ T cells respond to oral antigen may have important clinical applications as recent studies have successfully sensitized immune responses to oral carcinogens and enhanced mucosal immunity in diseases such as AIDS. Recent studies in patients with multiple sclerosis and rheumatoid arthritis have shown that oral feeding of tissue proteins may provide a new approach to decreasing disease recurrences in autoimmune diseases. Therefore, we will focus our studies on examining critical aspects of the mucosal T cell response to exogenous antigen. We will utilize a T cell receptor transgenic murine model specific for a peptide of chicken ovalbumin (Ova). By studying intestinal T cells in control and Ova-fed mice we will be able to examine the factors which influence the development of intestinal T cell responses.